Clinical effectiveness of a mite allergen-impermeable bed-covering system in asthmatic mite-sensitive patients

BACKGROUND: Exposure to allergens plays a role in the development of bronchial hyperresponsiveness and in the chronic inflammatory response seen in asthmatic patients. House dust mites (HDMs) are an important source of allergen. Reduction of these allergens might lead to better lung function and reduction of asthma symptoms. OBJECTIVE: The effect of HDM-impermeable covers on HDM allergen levels, peak flow values, and asthma symptoms were measured. Therefore a randomized clinical trial was carried out. METHODS: Fifty-two allergic asthmatic patients were randomly allocated to use the HDM-impermeable or placebo covers. During the study period, daily peak flow and asthma symptom scores were recorded. Dust samples were taken from the mattresses. RESULTS: We observed a significant reduction in HDM allergen levels on the mattresses after encasing them with HDM-impermeable covers (reduction of 87% of Der p 1 in micrograms per gram of dust; P <.001). Baseline symptoms were so low that no improvement could be established. Morning peak expiratory flow is significantly higher in the intervention group compared with that seen in the placebo group during the study period (beta=20.2; P <.01). CONCLUSIONS: HDM-impermeable covers significantly decreased the level of HDM allergens. Furthermore, morning peak flow was significantly increased during the intervention period. This study indicates that HDM allergen-avoidance measures might have beneficial effects on allergen reduction and asthma outcome.     

Enhanced Human Neutrophil Vitamin C Status,Chemotaxis and Oxidant Generation Following Dietary Supplementation with Vitamin C-Rich SunGold Kiwifruit

Neutrophils are the body’s primary defenders against invading pathogens. These cells migrate to loci of infection where they engulf micro-organisms and subject them to an array of reactive oxygen species and antimicrobial proteins to effect killing. Spent neutrophils subsequently undergo apoptosis and are cleared by macrophages, thereby resolving the inflammatory episode. Neutrophils contain high concentrations of vitamin C (ascorbate) and this is thought to be essential for their function. This may be one mechanism whereby vitamin C enhances immune function. The aim of our study was to assess the effect of dietary supplementation with vitamin C-rich SunGold kiwifruit on four important functions of neutrophils: chemotaxis, oxidant generation, extracellular trap formation, and apoptosis. Fourteen young men (aged 18–30 years) with suboptimal plasma vitamin C status (<50 μmol/L) were supplemented for four weeks with two SunGold kiwifruit/day. Plasma vitamin C status was monitored weekly and neutrophil vitamin C levels were assessed at baseline and post-intervention. Neutrophil function assays were carried out on cells isolated at baseline and post-intervention. Plasma vitamin C levels increased to >70 μmol/L (p < 0.001) within one week of supplementation and there was a significant increase in neutrophil vitamin C status following four weeks’ intervention (p = 0.016). We observed a significant 20% increase in neutrophil chemotaxis post-intervention (p = 0.041) and also a comparable increase in oxidant generation (p = 0.031). Supplementation did not affect neutrophil extracellular trap formation or spontaneous apoptosis. Our data indicate that supplementation with vitamin C-rich kiwifruit is associated with improvement of important neutrophil functions, which would be expected to translate into enhanced immunity.     

Glucose tolerance,insulin sensitivity,and insulin secretion in children born small for gestational age

Intrauterine growth retardation is associated with an increased risk of developing adult diseases, such as noninsulin-dependent diabetes mellitus (NIDDM). NIDDM could result from a decreased insulin sensitivity or a reduced insulin secretion or a combination of both. Glucose tolerance, insulin sensitivity, and insulin secretion were studied in prepubertal children born small for gestational age (SGA). Twenty-nine SGA children with a mean age of 9.1 +/- 1.1 yr and 24 children born appropriate for gestational age (AGA), with a mean age of 9.0 +/- 1.1 yr, were studied. All children were born at term and were prepubertal. Children were studied on two separate days after 12 h of overnight fasting. Day 1: Glucose tolerance was studied with an oral glucose tolerance test. AUC(ins0-120 min)/AUC(gluc0-120 min) was used to estimate beta-cell function in the two groups. Day 2: A hyperinsulinemic euglycemic clamp study was performed to determine insulin sensitivity (M-value). Glucose tolerance and beta-cell function were not different between the two groups. M-value in SGA children was significantly lower than M-value in AGA children: 12.9 +/- 4.0 mg/kg.min vs. 15.6 +/- 2.3 mg/kg.min [P = 0.009; after adjustment for appropriate gestational age body mass index (BMI), P = 0.001]. The M-value tended to be higher in SGA children without catch-up growth compared with SGA children with catch-up growth (15.8 +/- 4.3 vs. 12.3 +/- 3.8 mg/kg.min; P = 0.079) and was comparable to AGA controls (15.6 +/- 2.3 mg/kg.min). The M-value in SGA children who had shown catch-up growth was comparable to AGA children (13.4 +/- 3.4 vs. 15.6 +/- 2.3 mg/kg.min; P = 0.06), provided they had a BMI of 17 kg/m(2) or less. However, the SGA children with catch-up growth and a BMI greater than 17 kg/m(2) were those having the lowest M-values (9.3 +/- 3.4 mg/kg.min). In conclusion, during oral glucose tolerance tests, no differences were found in glucose tolerance and beta-cell function between the SGA and AGA groups. However, the hyperinsulinemic clamp showed a reduced insulin sensitivity in SGA children, which may contribute to the enhanced risk of developing NIDDM in adult life, especially in SGA children with catch-up growth and a high BMI. The implications of our findings in relation to height are unclear, but might be of potential importance when considering GH treatment. In addition, interventions to improve fetal growth and to control obesity in childhood seem to be important factors in the prevention of NIDDM.     

D-dimer levels in assessing severity and clinical outcome in patients with community-acquired pneumonia. A secondary analysis of a randomised clinical trial

BackgroundD-dimer levels are in several studies elevated in patients with CAP. In this study we assess the use of D-dimer levels and its association with severity assessment and clinical outcome in patients hospitalised with community-acquired pneumonia.MethodsIn a subset of randomised trial patients with community-acquired pneumonia serial D-dimer levels was analysed. CURB-65 scores were calculated at admission.ResultsA total of 147 patients were included. D-dimer levels at admission were higher in patients with severe CAP (2166 ± 1258 versus1630 ± 1197 μg/l, p = 0.03), with clinical failure at day 30 (2228 ± 1512 versus 1594 ± 1078 μg/l, p = 0.02) and with early failure (2499 ± 1817 μg/l versus 1669 ± 1121 μg/l, p = 0.01). Non-survivors had higher D-dimer levels (3025 ± 2105 versus 1680 ± 1128 μg/l, p = 0.05). None of the 16 patients with D-dimer levels < 500 μg/l died. In multivariate analysis D-dimer levels were not associated with clinical outcome. D-dimer levels have poor accuracy for predicting clinical outcome at day 30 (AUC 0.62, 95% CI 0.51–0.73) or 30 day mortality (AUC 0.71 (95% CI 0.51–0.91)). Addition of D-dimer levels to CURB-65 did not increase accuracy. No differences were observed in serial D-dimer levels between patients with clinical success or failure at day 30.ConclusionD-dimer levels are elevated in patients with CAP. Significantly higher D-dimer levels are found in patients with clinical failure and with severe CAP. D-dimer levels as single biomarker or as addition to the CURB-65 have no added value for predicting clinical outcome or mortality. D-dimer levels < 500 μg/l may identify candidates at low risk for complications.     

Brood pouch-mediated polystyrene nanoparticle uptake during Daphnia magna embryogenesis

Nanoplastic debris is currently expected to be ubiquitously distributed in aquatic environments and an emerging environmental issue affecting organisms across trophic levels. While ingestion of particles receives most attention, other routes of uptake and cellular accumulation remain unexplored. Here, the planktonic filter feeder Daphnia magna was used to track routes of uptake and target tissues of polystyrene nanoparticles (PSNPs). A sublethal concentration of 5?mg L^?1 fluorescent PSNPs (25?nm) was used to monitor accumulation in adult animals as well as their embryos in the open brood pouch. A time series throughout embryonic development within the brood pouch revealed accumulation of PSNP in or on lipophilic cells in the early stages of embryonic development while the embryo is still surrounded by a chorion and before the beginning of organogenesis. In contrast, PSNP particles were neither detected in the gut epithelium nor in lipid droplets in adults. An ex vivo exposure of embryos to PSNP demonstrated a similar accumulation of PSNP in or on lipophilic cells, illustrating the likelihood of brood pouch-mediated PSNP uptake by embryos. By demonstrating embryo PSNP uptake via the brood pouch, data presented here give novel insights in bioaccumulation of nanoparticles and likely other lipophilic contaminants. Since this uptake route can occur within a diverse array of aquatic organisms, this study warrants consideration of brood pouch-mediated accumulation in efforts studying the hazards and risks of nanoparticle contamination.     

Survey of the temporal changes in HIV-1 replicative fitness in the Amsterdam Cohort

Changes in virulence and fitness during an epidemic are common among pathogens. Several studies have shown that HIV fitness increases within a patient during disease progression, while bottlenecks, such as sexual transmission, immune pressure and drug treatment can reduce fitness. In this study, we analyzed how these opposing forces have shaped HIV-1 fitness over time. Therefore, we compared the replicative fitness of HIV-1 isolates from newly infected untreated individuals, diagnosed for HIV-1 infection early in the AIDS epidemic in Amsterdam, the Netherlands, with more recent isolates. Twenty-five early and late HIV-1 isolates, carefully matched for seroconversion time, were competed head-to-head in a dual infection/competition assay, employing peripheral blood mononuclear cells. In contrast with previous studies, we observed a trend of increasing fitness over time in the HIV epidemic of Amsterdam. Apparently, the bottleneck, occurring with each transmission event, does not completely reset the fitness increase acquired during disease progression.